Cystic fibrosis (CF) is a genetic disease caused by a defective cystic fibrosis transmembrane conductance regulator (CFTR) gene. Because the most serious clinical manifestations of the disease are due to defects in airway epithelial cells, it is believed that it may be possible to use viral mediated gene therapy directed at airway epithelial cells to correct the problem. Adeno-associated virus (AAV) is a non-pathogenic human DNA virus which can integrate into human cells with high efficiency. Since AAV is normally found associated with adenovirus, airway epithelial cells may be a normal target for AAV integration. Therefore, in this application we propose to test the feasibility of using AAV as a viral vector for the delivery and integration of a functional CFTR gene into airway epithelial cells. Specifically, we propose to: 1) isolate and test AAV recombinant viruses that contain the CFTR CDNA, 2) make an AAV recombinant virus carrying a marker gene to measure the frequency of transduction in primary airway epithelial cells, and 30 develop new methods for growing pure AAV recombinant viruses.